The Epigenetics Revolution

It’s all very well to think about how this could happen, but really we need to know if acquired characteristics can actually be inherited in this way. Not how does it happen, but the more basic question of does it happen? Remarkably, there appear to be some specific situations where this is indeed taking place. This doesn’t mean that Darwinian/Mendelian models are wrong, it just means that, as always, the world of biology is more complicated than we imagined.

The scientific literature on this contains some confusing terminology. Some early papers refer to epigenetic transmission of an acquired trait but don’t seem to have any evidence of DNA methylation changes, or histone alterations. This isn’t sloppiness on the part of the authors. It’s because of the different ways in which the word epigenetics has been used. In the early papers the phrase ‘epigenetic transmission’ refers to inheritance that cannot be explained by genetics. In these cases, the word epigenetic is being used to describe the phenomenon, not the molecular mechanism. To try to keep everything a little clearer, we’ll use the phrase ‘transgenerational inheritance’ to describe the phenomenon of transmission of an acquired characteristic and only use ‘epigenetics’ to describe molecular events.

Some of the strongest evidence for transgenerational inheritance in humans comes from the survivors of the Dutch Hunger Winter. Because the Netherlands has such excellent medical infrastructure, and high standards of patient data collection and retention, it has been possible for epidemiologists to follow the survivors of the period of famine for many years. Significantly, they were able to monitor not just the people who had been alive in the Dutch Hunger Winter, but also their children and their grandchildren.

This monitoring identified an extraordinary effect. As we have already seen, when pregnant women suffered malnutrition during the first three months of the pregnancy, their babies were born with normal weight, but in adulthood were at higher risk of obesity and other disorders. Bizarrely, when women from this set of babies became mothers themselves, their first born child tended to be heavier than in control groups[40][41]. This is shown in Figure 6.1, where the relative sizes of the babies have been exaggerated for clarity, and where we’ve given the women arbitrary Dutch names.

^{Figure 6.1 The effects of malnutrition across two generations of children and grandchildren of women who were pregnant during the Dutch Hunger Winter. The timing of the malnutrition in pregnancy was critical for the subsequent effects on body weight.}

The effects on the birth weight of baby Camilla shown at the bottom left are really odd. When Camilla was developing, her mother Basje was presumably healthy. The only period of malnutrition that Basje had suffered was twenty or more years earlier, when she was going through her own first stages of development in the womb. Yet it seems that this has an effect on her own child, even though Camilla was never exposed to a period of malnutrition during early development.

This seems like a good example of transgenerational (Lamarckian) inheritance, but has it has been caused by an epigenetic mechanism? Did an epigenetic change (altered DNA methylation and/or variations in histone modifications) that had occurred in Basje as a result of malnutrition during her first twelve weeks of development in the womb get passed on via the nucleus of her egg to her own child? Maybe, but we shouldn’t ignore that there are other potential explanations.

For example, there could be an unidentified effect of the early malnutrition which means that when pregnant, Basje will pass more nutrients than normal across the placenta to her foetus. This would still create a transgenerational effect – Camilla’s increased size – but it wouldn’t be caused by Basje passing on an epigenetic modification to Camilla. It would be caused by the conditions in the womb when Camilla was developing and growing (the intra-uterine environment).